The predictive value of GSTT1 polymorphisms in predicting the early response to induction BCG therapy in patients with non-uscle invasive bladder cancer

Introduction: We evaluated the predictive value of glutathione S transferase mu (GSTM1) and theta (GSTT1) polymorphisms in early response to bacillus Calmette-Guerin (BCG) induction therapy in patients with primary non muscle invasive bladder cancer. Methods: GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction using blood genomic DNA from 135 patients with primary non muscle invasive bladder cancer who were being treated with a single induction course of BCG. BCG nonresponsiveness (early BCG failure) was defined as a tumor recurrence or progression within 12 months after BCG induction therapy. The predictive value of GST polymorphisms was evaluated by Kaplan-Meier analysis and multivariate logistic regression models. Results: Patients carrying a GSTT1-positive genotype demonstrated a higher likelihood of early BCG failure regardless of cigarette smoking. After stratification based on the tumor stage and grade, the high-risk group (T1G3) with a GSTT1-positive genotype showed a 14-fold higher risk of early BCG failure compared with those with a GSTT1-null genotype. In a combined analysis of 2 genes, the GSTT1-positive/GSTT1-null genotype had a higher risk of BCG nonresponsiveness compared with the GSTT1-null/GSTM1-null genotype (odds ratio = 4.17, 95% CI: 1.54-11.26). By multivariate logistic regression analysis, the GSTT1-positive genotype was an independent predictor of early BCG failure (odds ratio = 3.67, 95% CI: 1.61-8.38). Kaplan-Meier estimates revealed a significant difference in disease-free survival depending on the GSTT1 genotype (log rank test, P = 0.038). Conclusions: The results of this study suggest that the GSTT1-positive genotype is an independent predictor of early BCG failure. These results can help determine whether patients would benefit from adjuvant BCG treatment or may require more aggressive alternative therapies. (C) 2014 Elsevier Inc. All rights reserved.